Deesterification of aromatic compounds



Patented May 19, 1953 noraetiomofiDelaware Ndlli'awihg, Applicationbecember2311949, seriamo. 1s4;sss=

4:01am; (Cl. 260-5623) invention relates to= the de-testeri-ficatiom OESJIOmBAfiQF compounds; and; moreapa-rticularlyg to a method for de-esterifying on freeina -sali' geninor asubstituted-saligenin from saligenin diacetatemr assubstituted saligenirr diacetate.

' The needifor the discovery of a relatively inemllmsivev method' for: producing?SF-fiiiorflsalitayi alflehydeihasyrecently appearedl 'Ihe -needarose assaal'esultiof thezworw ofTs'umakia (see J 3 Chem;

2i i Y Theerestztof theastructurezofttheiimaterial.Athattiss deeesterifiedt in: the practice of: the inventiom relatively unmipertantz Each substituent if anyz; is: attachedv tothee3e; 455g or.:v6t+carbomatom:a

halogen a. lower; alkyl'; orrlowenalkoxyi radicals, amhenyl ior; 'phenoxyradical; ,or: amaralkyle, aryl', alkaroxy: or: aralkoxy radical, having: not: more thanten carbomatoms: ("fliower alks'i, and;

J 58%; 1283?: (1937 31): andiCalvim (see :JZ 10 lcwerralkoxm asausedzhereinirnefer to: radicalsg Am. Chem. Soc. 68, 2254. (19459): Tsumaki-l showedithatithegcotialtechelate of the 'Schifis:; -ase frmmsalicylaldehyde andgethylene diamine I would and that' the absorption was rehavingrgnot more-than :fourtzcalfbenz atomsz) As 1 is hereinbefore: indicated; they; 1;-hydroxy methyl-zt-phenol, is deeesterified according;;,.to the invention by refluxing a mixture thereon-with:

versible; andscalvirrfifoundithatwtheacobaltchelata methanol. It is impprtan that 'arelatively lar e otqtheszschiffifsabaseifromiikefiuorosalicylaldehyde: andz iethyleneaqdiamine wasi-zparticula-rlysadvanta+ geous as 'providing a convenient meansior separating xys m f jomi .theii nitrogen ofrthe-v air. A

3$fiuorosalicylaldehydm resulted" inzthe. discovery ofv: aniefiicacions way: of? producing; fiechloro-ae fluoxosaiig n-imdiacetatesand:relatedcomnoundsi;V Harvevematt mntseto; deresterifyp the: diaeetates;

produced by this method by ordinary means; ingstheydistillationhf,the;methyl:alcOhohmethxlL.

PQZOWQJUMHQQESSWL. ThGL'CQMQWdfiFMB sufiici-entlw ensitiv to strong reasentssandnelevated; temperatures that de-esterification could notgbe accomplished in reasonable yields by ordinary methods.

The principal obiect of the invention is to provide a method for de-esterifying saligenin diacetate and substitutedfsaliggnin;diacetates. More specific objects and advantages are apparent from the description which illustrates and discloses but does not limit the invention.

According" to the invention the diacetate of a 1-hydroXymethyl 2-phenol is de esterified. The deeester fication" is accomplished? by 'refiuxinga mixture-ofthediacetate of the-l"-hydroxymethyl- 2phenol with methanol'in the---presence-=of=a strdngmmerai acid? and distilling; low-boiling material formeduntil the head temperature reaches the boiling temperatureof methanol:-

structure 0f;'-the=-' compounds that are-= de--- esterifled 'accordingctortheinvention may be-more cleariy junderstood by:'yreferenceto--the aim-lowing; schematiceformulas ratio" ofcmethanolz; to; the-diacetate 0f; the-,-,1 hy -t dr0xymethyl-2rnhenolheemphyed; in- ,theeprac-t tice ofqtheinvention The:lrhyi mxyj ethy).12,? phenols area heat.v sensitive accordingly; thew;

- seammfor:aminexpensiveimethod forrproducing.t 20 amount-10f methanol em-p10y.dis--.the.sumr of: (-1

acetate azeotrepe, B. P. 54 C., and (3) anlamountw oflmethanolzsufficient tomaintain the;;;1=hydroxy methyl-2 -phenolin solution :without; .overeheatw: ing, in the course of the reaction. Ordinarily it is essential that the mol ratio of methanol to the diacetate be,a t least, about 10:1, Usually it ..is economically disadvantageous that the"mo1"rati;ot behigher than about-25:1; andmostdesiredvth'at v it be about20zl: v Althoughitis-possibleto -conduct the-de-esterifi'cation of the invention underreduced pressurega this is :ordinari'ly undesirable because-:oflthe ma creased F cost involved.: Superatmosph'eric: pres sures, because of the increased? temperaturescine best e procedurew usually a is:; to carry: out thfil: dew esterification; atatmosphericupressure. Theamaie terial volatilized; the early;- part1. of; the: dee esterificationi is; principally: thee-methyl alcohols methylaacetate:azeotrope; The materia-Lwvappr,- izedzzia-removect slowly; fromthe reaction :vesseh. Whemthewapor ,temperature= rises subs.tantially; abiove: the-boilingepoint; of the :azeotrope (elv r.. from-4; C; ,tot.-5--G;vabove) all vapors areecondensed;.andritheqcondensate returned to :the: re=- "action vessel (1. e., total reflux is used). If the. removaliof{vapors-masubeem:sufiicientlyrfaststhat a;substantialpropontion.otitliezazeotropegremainsa in the reaction: vesseLa the temperature of: thin 55;; vapors will drop substantially to the boilingtem volved; area disadvantageous. a Accordingly; the;

perature of the azeotrope; if not, the temperature will remain approximately constant when the removal of vaporized material is discontinued. Removal from the system of materials vaporized is continued until there is no indication of the presence of additional low boiling azeotrope, after which point in the distillation a small quantity of vapor is removed until the head temperature reaches the boiling temperature of methyl alcohol. De-esterification. is. then found to have proceeded to such an extentthat the pure 1-hydroxymethyl-2-phenol can be recovered by pouring the reaction mixture into distilled water. The desired product crystallizes in a pure form.

As is heretofore stated, the de-esterification is accomplished in the presence are strong mineral acid. It is usually preferred that the strong minwas crystallized by making the filtrate slightly alkaline, concentrating it to a volume of 500 cc., acidifying, and adding a few seed crystals of 5- chloro-3-fluorosaligenin. The total recovery of 5- chloro-3-fiuorosaligenin amounted to 175 grams, which corresponds to a 99 per fcent yield based upon the 5-chloro-3-fluorosaligenin diacetate used.

Eznample 2 A procedure similar to that described in Example 1 was used to de-esterify 3,5-dichlorosaligenin diacetate. ".The 3,5-dichlorosaligenin diacetate (138 grams), methanol (250 grams) and benzene sulfonic acid (0.1 gram) were refluxed f Y and the azeotro'pe was distilled. When the methyl eral acid that is used be one sufiiciently soluble in i the reaction solution thatfit is not distilled therefrom in the course of the refluxing; otherwise, additions of the acid must be made during reaction. Sulfuric acid and sulfonic acids are particularly desirable, especially aryl sulfonic acids (e.g., benzene sulfonic acid, toluene sulfonic acids, xylene sulfonic acids, andthe like). The amount of the strong mineral acid that is used may vary from about 0.5 per cent to about 3 per cent. (The terms percent and parts are used herein to refer to per cent and parts by weight unless otherwise indicated.) Itis' usually preferred that the amount of strong mineral acid employed be about 1 per cent of the diacetate present.

The method of the invention is particularly advantageous because of the characteristics of the l-hydroxymethyl-Z-phenols and their diacetates. The heat sensitivity of these compounds not only makes de-esterification by ordinary means impractical, but also makes purification (e. g., by recrystallization or distillation) of the l-hydroxymethyl-2-phenol virtually impossible.

Accordingly,if it is desired to obtain a pure product,f--it is necessary to conduct a slow de-esterifi cation so that substantially quantitative reaction is achieved.

The following examples illustrate, but are not to be construed as limiting the invention:

I I A Epample 1 According to the invention the diacetate of a l-hydroxymethyl-Z-phehol was de-esterified according to the following procedure:

5 chloro 3 fluorosaligenin diacetate 1 (260 grams), methanol (1200 cc.) and benzene sulfonic acid (1 gram) were mixed and heated to reflux A slow distillation through a four foot column (using. a reflux ratio of :1) Was then started. This distillation was discontinued When the head temperature of the vapors exceeded 64 C., at which time the total distillate (principally the methyl alcohol-methyl acetate amounted to 900 cc. The residue in the still was then diluted with water to make a total volume of azeotrope) three liters. A few seed crystals of previously pre pared 5-chloro-3-fluorosaligenin were added thereto, and the desired product, which crystallized immediately, was separated from the liquid l by filtration and was air dried. Further product 1 The preparation of 5-chloro 3-fluorosaligenin diacetate is disclosed in the application of Edgar C, Britton and James D.

Head entitled Production of '3-fluorosalicyl aldehyde filed concurrentlyherewith, now U. S. Patent I acetate had been distilled, cold water (1500 cc.) was added to the residue in the still. White crystals of 3,5-dichlorosaligenin precipitated immediatelyand were recovered in-pure formmand in a substantially theoretical yield by'filtration and air drying. 1

Iolaim:

1. A method of de-esterifying 5-ch1oro-3'- fluorosaligenin diacetate which comprises heating a mixture thereof with methanol at a reflux.-. ing temperature in the presence of astrongacid, and distilling, low-boiling material formedzuntilv the head temperature reaches the boiling 'tem-' perature of methanol.

2. A method of de-esterifying, 3,5-dichloro; saligenin diacetate which comprises heating 'a mixture thereof with methanol at a refluxing tem-i perature in the presence of a strong acid, and distilling low-boiling material formed until the. head temperature reaches the boiling temperature of methanol,

3. A method of de-esterifying a 3,5-dihalosaligenin diacetate which comprises heating a. mixture thereof with methanol at a refluxin ii temperature in the presence of a strong acid, and" distilling low-boiling material'formed until the head temperature reaches the boiling temperature of methanol.-

4. A method of de-esterifying the diacetate or a l-hydroxy methyl-z-phenol corresponding "to:

the formula 0 HaCHI O CH reaches the boiling temperature of methanol.

JAMES D. HEAD.

References Cited mtiiembftnm patent Varvoglis, Ben-der deut. chem, GeselL," vol. 713, pp. 2488-92 (1938) 

1. A METHOD OF DE-ESTERIFYING THE DIACETATE OF A 1-HYDROXY METHYL-2-PHENOL CORRESPONDING TO THE FORMULA 